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GDM PATHOPHYSIOLOGY & EPIDEMIOLOGY

GDM PATHOPHYSIOLOGY & EPIDEMIOLOGY. BY: SH.ALAMDARI, MD ASSOCIATE PROFESSOR OF INTERNAL MEDICINE, ENDOCRINOLOGY & METABOLISM SBMU, RIES. Outline. Definition? Normal physiology of pregnancy? Review of pathophysiology of GDM? Risk factors of GDM? Reported prevalence in Iran?

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GDM PATHOPHYSIOLOGY & EPIDEMIOLOGY

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  1. GDM PATHOPHYSIOLOGY & EPIDEMIOLOGY BY: SH.ALAMDARI, MD ASSOCIATE PROFESSOR OF INTERNAL MEDICINE, ENDOCRINOLOGY & METABOLISM SBMU, RIES

  2. Outline Definition? Normal physiology of pregnancy? Review of pathophysiology of GDM? Risk factors of GDM? Reported prevalence in Iran? Impact of new criteria on prevalence of GDM? Conclusion? Dr. sh. Alamdari

  3. Definition Historically, the term “gestational diabetes” has been defined as onset or first recognition of abnormal glucose tolerance during pregnancy. The American College of Obstetricians and Gynecologists (ACOG) continues to use this terminology Dr. sh. Alamdari

  4. Definition • In recent years, the International Association of Diabetes and Pregnancy Study Group (IADPSG), the American Diabetes Association (ADA), the World Health Organization (WHO), and others have attempted: • to distinguish women with probable preexisting diabetes that is first recognized during pregnancy from those whose disease is a transient manifestation of pregnancy-related insulin resistance Dr. sh. Alamdari

  5. Definition This change acknowledges the increasing prevalence of undiagnosed type 2 diabetes in nonpregnant women of childbearing age. These organizations typically use the term “gestational diabetes” to describe diabetes diagnosed during the second half of pregnancy, and terms such as “overt diabetes” or “diabetes mellitus in pregnancy” to describe diabetes diagnosed early in pregnancy, when the effects of insulin resistance are less prominent. Dr. sh. Alamdari

  6. Several adverse outcomes associated with diabetes during pregnancy Preeclampsia Hydramnios Macrosomiaand large for gestational age infant Fetal organomegaly (hepatomegaly, cardiomegaly) Maternal and infant birth trauma Operative delivery Perinatal mortality Neonatal respiratory problems and metabolic complications (hypoglycemia, hyperbilirubinemia, hypocalcemia, erythremia) Dr. sh. Alamdari

  7. 10 Risk factors Personal history of impaired glucose tolerance or gestational diabetes in a previous pregnancy Member of one of the following ethnic groups, which have a high prevalence of type 2 diabetes: Hispanic-American, African-American, Native American, South or East Asian, Pacific Islander Family history of diabetes, especially in first degree relatives Prepregnancyweight ≥110 percent of ideal body weight or BMI >30 kg/m2, significant weight gain in early adulthood and between pregnancies, or excessive gestational weight gain Dr. sh. Alamdari

  8. 10 Risk factors Maternal age >25 years of age Previous delivery of a baby >9 pounds (4.1 kg) Previous unexplained perinatal loss or birth of a malformed infant Maternal birthweight >9 pounds (4.1 kg) or <6 pounds (2.7 kg) Glycosuria at the first prenatal visit Medical condition/setting associated with development of diabetes, such as metabolic syndrome, polycystic ovary syndrome (PCOS), current use of glucocorticoids, hypertension Dr. sh. Alamdari

  9. Risk factors Obstet Gynecol Clin N Am 37 (2010) 255–267 Dr. sh. Alamdari

  10. Women at low risk of gestational diabetes are • younger (<25 years of age), • non-Hispanic white, • with normal BMI (<25 kg/m2), • no history of previous glucose intolerance or adverse pregnancy outcomes associated with gestational diabetes, and • no first degree relative with diabetes. • Only 10 percent of the general obstetric population in the United States meets all of these criteria for low risk of developing gestational diabetes, which is the basis for universal rather than selective screening Dr. sh. Alamdari

  11. Maternal physiologic adaptations facts Pregnancy is associated with major changes in metabolic processes and endocrine function. Growth and development of the fetus. Providing the fetus with adequate stores of energy and substrates needed for transition to extra uterine life. Maternal needs for increased physiologic demands of pregnancy. Providing energy and substrate stores for pregnancy , labor and lactation. Dr. sh. Alamdari

  12. Physiology of pregnancy Pregnancy is primarily an anabolic state: 1- Increased food intake and appetite. 2- Around 3.5 kg of fat is deposited. 3- New protein synthesis is about 900 g. 4- The energy cost of reproduction is estimated at 75000- 85000 Kcal. Dr. sh. Alamdari

  13. 1-Basal Metabolic Rate during pregnancy Dr. sh. Alamdari

  14. 2-Insulin metabolism during pregnancy Insulin degradation is increased by liver and placenta Insulin secretion is increased ( beta cell hypertrophy) due to insulin resistance. Dr. sh. Alamdari

  15. Insulin requirement during pregnancy Metzger BE , Freinkel N.Biol Neonate 1987 ; 51 : 78 – 85 . Dr. sh. Alamdari

  16. 3- Hepatic glucose production a) Early pregnancy: Insulin sensitivity Glucose production Lipogenesis Anabolic state for mother and fetus Dr. sh. Alamdari

  17. b) Late pregnancy: Anti-insulin hormones Increase insulin resistance Beta cell hypertrophy Hyperinsulinemia Increase insulin degradation Lipolysis Accelarated starvation ( hyperketonemia ) Hypoaminoacidemia ( fetus storage ) Anabolic state ( fetus ) Catabolic state in mother Dr. sh. Alamdari

  18. Anti-insulin hormones of pregnancy HPL: The strogest hormone GH like effect Lipolysis - Liopogenesis Insulin resistance Progestrone- Estrogen Insulin resistance – beta cell hypertrophy – cortisol secretion Cortisol ( free and total ) Insulin resistance, IRS-1 Dr. sh. Alamdari

  19. Prolactin -Placenta GHv. GH like effect beta cell hypertrophy and insulin secretion. Leptin – Adipokines Insulin resistance TNF α - INL6 …( ? ) Mills JL, et al. Metabolism 1998 ; 47 : 1140 – 1144 Dr. sh. Alamdari

  20. Early pregnancy Increased glucose-stimulated insulin secretion Unchanged or enhanced peripheral (muscle) insulin sensitivity Unchanged basal hepatic glucose production Normal or slightly improved glucose tolerance Normal sensitivity to the blood glucose–lowering effect of exogenously administered insulin. Late pregnancy Rising concentrations of several diabetogenic hormones Increased peripheral insulin resistance Progressive increase in basal & postprandial insulin (up to 2 fold in third trimester) lower insulin action in late normal pregnancy than in non pregnant women (50-70%) Basal endogenous hepatic glucose production increases by 16–30% Dr. sh. Alamdari

  21. Maternal adaptation The maternal response is characterized by a switch from carbohydrate to fat utilization that is facilitated by both insulin resistance and increased plasma concentrations of lipolytichormones After an overnight fastthe maternal fasting capillary whole blood glucose concentration falls ,while plasma ketone and free fatty acid concentrations rise Mother preferentially use fat (eg, free fatty acids, triglycerides, ketone bodies) Preserve much of the available glucose and amino acids (especially alanine) for the fetus Dr. sh. Alamdari

  22. Maternal-Fetal metabolism Anabolic phase: - Normal or increased sensitivity to insulin - lower plasmaglucose level - lipogeneses, glycogen stores increases Catabolicphase(Accelerated starvation): - Maternal insuln resistance - Increased transport of nutritients trough placental membrane - lipolysis Cousins L. Diabetes 1991 ; 40 ( Suppl-2 ): 39 – 43 .

  23. Pathophysiology of GDM • The development of gestational diabetes is associated with a much greater severity of insulin resistance than normal pregnant women. • The degree of insulin resistance seems to be influenced by obesity & inheritance. • Gestational diabetes mellitus occurs when a woman's pancreatic function is not sufficient to overcome the insulin resistance. • GDM occurs as a result of a combination of insulin resistance and decreased insulin secretion. Barbour LA et al. Diabetes Care 2007 ; 30 ( Suppl2 ): 112 – 119. Dr. sh. Alamdari

  24. Clinical implications Pregnancy as a state of facilitated anabolism. Pregnancy as a state of accelerated starvation. Pregnancy as a state of diabetogenic state. Dr. sh. Alamdari

  25. Prevalence GDM complicates approximately 1% to 14% of all pregnancies. ( 5% - 6% ) In low-risk populations, such as those found in Sweden, the prevalence in population-based studies is lower than 2%. In high-risk populations, such as the Native American Cree, Northern Californian Hispanics and Northern Californian Asians, reported prevalence rates ranging from 4.9% to 12.8%. CurrDiab Rep (2010) 10:224–228 Dr. sh. Alamdari

  26. Reasons for differences in reported prevalence Different diagnostic criteria Different screening policies Different definitions, screening strategies and awareness of type 2 diabetes Maternal age Racial/ethnic composition of population ObstetGynecolClin North Am. 2007 June ; 34(2): Dr. sh. Alamdari

  27. This report is based on 36,403 KPCO singleton pregnancies occurring between 1994 and 2002 and examines trends in GDM prevalence among women with diverse ethnic backgrounds Diabetes Care 28:579–584, 2005 Dr. sh. Alamdari

  28. The prevalence of GDM among KPCO members doubled from 1994 to 2002 (2.1– 4.1%, P 0.001) Prevalence of GDM is increasing in a universally screened multiethnic population Given the etiology of type 2 diabetes , the observed increase probably reflects the well-documented obesity epidemic Dr. sh. Alamdari

  29. 92 153 1 Different protocol for diagnosis Dr. sh. Alamdari

  30. Aim: Impact of new IADPSG criteria on diagnosis of GDM compared with ADA criteria Diabetes Care 2010 33:2018–2020, Dr. sh. Alamdari

  31. Results ADA criteria identified 12.9%women with GDM IADPSG criteria identified 37.7% women with GDM The IADPSG criteria increased GDM prevalence nearly threefold Dr. sh. Alamdari

  32. Epidemiological studies in Iran Larijani B, et al. Cost analysis of different screening strategies for gestational diabetes mellitus. EndocrPract 2003;9:504–509. Keshavarz M, et al. Gestational diabetes in Iran: incidence, risk factors and pregnancy outcomes. Diabetes Res ClinPract 2005;69:279–286. HadaeghF , et al. Prevalence of gestational diabetes mellitus in southern Iran (Bandar Abbas City). EndocrPract 2005;11:313–318. Hossein-Nezhad A et al ,Prevalence of gestational diabetes mellitus and pregnancy outcomes in Iranianwomen.Taiwan J Obstet Gynecol. 2007 Sep;46(3):236-41 Maghbooli Z et al ,Relationship between leptin concentration and insulin resistance .HormMetab Res. 2007 Dec;39(12):903-7 Shirazian N et al, Comparison of different diagnostic criteria for gestational diabetes mellitus based on the 75-g oral glucose tolerance test: a cohort study . EndocrPract 2008 Apr;14(3):312-7 Shirazian N et al ,Screening for gestational diabetes: usefulness of clinical risk factors .Arch Gynecol Obstet. 2009 Dec;280(6):933-7 Dr. sh. Alamdari

  33. Dr. sh. Alamdari

  34. Conclusion Pregnancy is characterized by insulin resistance and hyperinsulinemia, thus it may predispose some women to develop diabetes. Gestational diabetes occurs when pancreatic function is not sufficient to overcome the insulin resistance created by changes in diabetogenic hormones during pregnancy. Prevalence of GDM in a population is reflective of the prevalence of type 2 diabetes in that population. The prevalence of GDM in Iran varies between 4.7% and 8.9% ,which represents a moderate prevalence rate. Based on increasing trend of obesity in Iran, it seems that the prevalence of GDM is also increasing . Practical bulletin , ACOG 2013 :137; 406- 416 Dr. sh. Alamdari

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